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(Stroke. 2003;34:849.)
© 2003 American Heart Association, Inc.

Original Contributions

Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke

A Case-Crossover Study

Armin J. Grau, MD, PhD; Sven Reiners, Cand Med; Christoph Lichy, MD; Florian Buggle, MD Andreas Ruf, MD, PhD

From the Neurology Department, University of Heidelberg, Heidelberg, and Center for Laboratory Medicine, Microbiology, Transfusion Medicine, Klinikum Karlsruhe (A.R.), Karlsruhe, Germany.

Correspondence to Armin J Grau, MD, PhD, Neurologische Klinik, Städtisches Klinikum Ludwigshafen a.Rh., Bremserstr. 79, D-67063 Ludwigshafen, Germany. E-mail graua{at}klilu.de

Background and Purpose— Combined antiplatelet agents may offer additive protection over single drugs after stroke. We investigated whether platelet activation is reduced under combined aspirin and clopidogrel compared with each drug alone.

Methods— In a case-crossover study, 31 patients with previous atherothrombotic or lacunar stroke who were treated with aspirin (100 to 300 mg/d) received clopidogrel (75 mg/d) and both aspirin and clopidogrel for 4 weeks. Platelet function in whole blood was studied after each treatment period and in healthy control subjects to assess activation-dependent antigens CD62p and CD63 by flow cytometry and collagen/epinephrine (CEPI-CT) and collagen/ADP (CADP-CT) closure times with the platelet function analyzer PFA-100, which investigates platelet-related function under shear stress.

Results— CD62p expression and CD63 expression were not different under the 3 treatment regimens. CD63 but not CD62p expression was lower in control subjects than in stroke patients regardless of the antiplatelet treatment (P<0.05). CEPI-CT was prolonged under aspirin and aspirin plus clopidogrel compared with clopidogrel monotherapy (P<0.0001). CADP-CT was longer under combination therapy than under aspirin (P=0.0009) or clopidogrel (P=0.0074) or in control subjects (P=0.0010), mainly because of strong prolongation in a patient subgroup (28%).

Conclusions— CD63 expression reflecting the release of platelet lysosomes is consistently increased after stroke and incompletely suppressed by treatment with aspirin, clopidogrel, or both. The strong prolongation of CADP-CT under combined aspirin and clopidogrel in a patient subgroup may indicate a lower risk of thrombosis but also a higher risk of hemorrhage. The predictive value of platelet activation parameters requires investigation in prospective studies.

Synergistic Antiplatelet Effects of Clopidogrel and Aspirin Detected With the PFA-100 in Stroke Patients

Bernd Jilma, MD, Guest Editor

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